by Jos Domen*, Amy Wagers** and Irving L. Weissman***

Blood and the system that forms it, known as the hematopoietic system, consist of many cell types with specialized functions (see Figure 2.1). Red blood cells (erythrocytes) carry oxygen to the tissues. Platelets (derived from megakaryocytes) help prevent bleeding. Granulocytes (neutrophils, basophils and eosinophils) and macrophages (collectively known as myeloid cells) fight infections from bacteria, fungi, and other parasites such as nematodes (ubiquitous small worms). Some of these cells are also involved in tissue and bone remodeling and removal of dead cells. B-lymphocytes produce antibodies, while T-lymphocytes can directly kill or isolate by inflammation cells recognized as foreign to the body, including many virus-infected cells and cancer cells. Many blood cells are short-lived and need to be replenished continuously; the average human requires approximately one hundred billion new hematopoietic cells each day. The continued production of these cells depends directly on the presence of Hematopoietic Stem Cells (HSCs), the ultimate, and only, source of all these cells.

Figure 2.1. Hematopoietic and stromal cell differentiation.

2001 Terese Winslow (assisted by Lydia Kibiuk)

The search for stem cells began in the aftermath of the bombings in Hiroshima and Nagasaki in 1945. Those who died over a prolonged period from lower doses of radiation had compromised hematopoietic systems that could not regenerate either sufficient white blood cells to protect against otherwise nonpathogenic infections or enough platelets to clot their blood. Higher doses of radiation also killed the stem cells of the intestinal tract, resulting in more rapid death. Later, it was demonstrated that mice that were given doses of whole body X-irradiation developed the same radiation syndromes; at the minimal lethal dose, the mice died from hematopoietic failure approximately two weeks after radiation exposure.1 Significantly, however, shielding a single bone or the spleen from radiation prevented this irradiation syndrome. Soon thereafter, using inbred strains of mice, scientists showed that whole-body-irradiated mice could be rescued from otherwise fatal hematopoietic failure by injection of suspensions of cells from blood-forming organs such as the bone marrow.2 In 1956, three laboratories demonstrated that the injected bone marrow cells directly regenerated the blood-forming system, rather than releasing factors that caused the recipients' cells to repair irradiation damage.35 To date, the only known treatment for hematopoietic failure following whole body irradiation is transplantation of bone marrow cells or HSCs to regenerate the blood-forming system in the host organisms.6,7

The hematopoietic system is not only destroyed by the lowest doses of lethal X-irradiation (it is the most sensitive of the affected vital organs), but also by chemotherapeutic agents that kill dividing cells. By the 1960s, physicians who sought to treat cancer that had spread (metastasized) beyond the primary cancer site attempted to take advantage of the fact that a large fraction of cancer cells are undergoing cell division at any given point in time. They began using agents (e.g., chemical and X-irradiation) that kill dividing cells to attempt to kill the cancer cells. This required the development of a quantitative assessment of damage to the cancer cells compared that inflicted on normal cells. Till and McCulloch began to assess quantitatively the radiation sensitivity of one normal cell type, the bone marrow cells used in transplantation, as it exists in the body. They found that, at sub-radioprotective doses of bone marrow cells, mice that died 1015 days after irradiation developed colonies of myeloid and erythroid cells (see Figure 2.1 for an example) in their spleens. These colonies correlated directly in number with the number of bone marrow cells originally injected (approximately 1 colony per 7,000 bone marrow cells injected).8 To test whether these colonies of blood cells derived from single precursor cells, they pre-irradiated the bone marrow donors with low doses of irradiation that would induce unique chromosome breaks in most hematopoietic cells but allow some cells to survive. Surviving cells displayed radiation-induced and repaired chromosomal breaks that marked each clonogenic (colony-initiating) hematopoietic cell.9 The researchers discovered that all dividing cells within a single spleen colony, which contained different types of blood cells, contained the same unique chromosomal marker. Each colony displayed its own unique chromosomal marker, seen in its dividing cells.9 Furthermore, when cells from a single spleen colony were re-injected into a second set of lethally-irradiated mice, donor-derived spleen colonies that contained the same unique chromosomal marker were often observed, indicating that these colonies had been regenerated from the same, single cell that had generated the first colony. Rarely, these colonies contained sufficient numbers of regenerative cells both to radioprotect secondary recipients (e.g., to prevent their deaths from radiation-induced blood cell loss) and to give rise to lymphocytes and myeloerythroid cells that bore markers of the donor-injected cells.10,11 These genetic marking experiments established the fact that cells that can both self-renew and generate most (if not all) of the cell populations in the blood must exist in bone marrow. At the time, such cells were called pluripotent HSCs, a term later modified to multipotent HSCs.12,13 However, identifying stem cells in retrospect by analysis of randomly chromosome-marked cells is not the same as being able to isolate pure populations of HSCs for study or clinical use.

Achieving this goal requires markers that uniquely define HSCs. Interestingly, the development of these markers, discussed below, has revealed that most of the early spleen colonies visible 8 to 10 days after injection, as well as many of the later colonies, visible at least 12 days after injection, are actually derived from progenitors rather than from HSCs. Spleen colonies formed by HSCs are relatively rare and tend to be present among the later colonies.14,15 However, these findings do not detract from Till and McCulloch's seminal experiments to identify HSCs and define these unique cells by their capacities for self-renewal and multilineage differentiation.

While much of the original work was, and continues to be, performed in murine model systems, strides have been made to develop assays to study human HSCs. The development of Fluorescence Activated Cell Sorting (FACS) has been crucial for this field (see Figure 2.2). This technique enables the recognition and quantification of small numbers of cells in large mixed populations. More importantly, FACS-based cell sorting allows these rare cells (1 in 2000 to less than 1 in 10,000) to be purified, resulting in preparations of near 100% purity. This capability enables the testing of these cells in various assays.

Figure 2.2. Enrichment and purification methods for hematopoietic stem cells. Upper panels illustrate column-based magnetic enrichment. In this method, the cells of interest are labeled with very small iron particles (A). These particles are bound to antibodies that only recognize specific cells. The cell suspension is then passed over a column through a strong magnetic field which retains the cells with the iron particles (B). Other cells flow through and are collected as the depleted negative fraction. The magnet is removed, and the retained cells are collected in a separate tube as the positive or enriched fraction (C). Magnetic enrichment devices exist both as small research instruments and large closed-system clinical instruments.

Lower panels illustrate Fluorescence Activated Cell Sorting (FACS). In this setting, the cell mixture is labeled with fluorescent markers that emit light of different colors after being activated by light from a laser. Each of these fluorescent markers is attached to a different monoclonal antibody that recognizes specific sets of cells (D). The cells are then passed one by one in a very tight stream through a laser beam (blue in the figure) in front of detectors (E) that determine which colors fluoresce in response to the laser. The results can be displayed in a FACS-plot (F). FACS-plots (see figures 3 and 4 for examples) typically show fluorescence levels per cell as dots or probability fields. In the example, four groups can be distinguished: Unstained, red-only, green-only, and red-green double labeling. Each of these groups, e.g., green fluorescence-only, can be sorted to very high purity. The actual sorting happens by breaking the stream shown in (E) into tiny droplets, each containing 1 cell, that then can be sorted using electric charges to move the drops. Modern FACS machines use three different lasers (that can activate different set of fluorochromes), to distinguish up to 8 to 12 different fluorescence colors and sort 4 separate populations, all simultaneously.

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2. Bone Marrow (Hematopoietic) Stem Cells [Stem Cell Information]

By Andrew Brown

Spinal cord injury typically causes permanent paralysis and is currently a condition without a cure. Could stem cell therapy provide hope?

American actor and activist Christopher Reeve will be remembered for his leading role in the 1978 blockbuster movie Superman. Sadly, he will also be remembered as a man whose tremendously active life, both on and off screen, was shattered by a catastrophic injury that left him paralysed from the neck downwards a state in which he remained until he died in 2004.

In May 1995, during an equestrian competition, Reeve was thrown headfirst off his horse. The weight of his body was thrust through his spine, breaking two of the vertebrae in his neck and causing extensive damage to his spinal cordw1.

What happened during his accident at the level of blood, bones, cells and molecules to cause his life-long paralysis? And how might research into new treatments based on stem cells offer hope for people paralysed by spinal cord injury? Could it help them to regain some control over their bodies and their lives?

What is spinal cord injury?

Your spinal cord is an information highway connecting your brain to the rest of your body (figure 1). Injuries to it are usually caused by sudden trauma, such as that sustained in sports or car accidents, and result in dislocation and / or breakage of vertebrae, which rip into the spinal cord tissue, damaging or severing axons. Sensation and motor control are lost below the level of the injury (figure 2).

Multiple cell types die at or near the site of the spinal cord injury, due tosecondary effects of the trauma, such as changes in blood supply, immune responses and an increase in free radicals and excitatory neurotransmitters (see box on the secondary effects of spinal cord injury).

Figure 1: Anatomy and function of the spinal cord. Click on image to enlarge.

The spinal cord is a soft, jelly-like structure that extends from the base of the brain to the lower back (A). It is 38 to 43 cm long and, at its maximum width, is about as wide as a thumb. It sits in a hollow channel that runs through the spinal columns 33 stacked vertebrae (B).

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Spinal cord injury: do stem cells have the answer? | Science ...

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Lot of 5 Serious Skin Care Replicate Renew Plant Stem Cell ...

November 22, 2013

Brett Smith for redOrbit.com Your Universe Online

Scientists from the University of Granada in Spain have announced the development of artificial skin, grown from umbilical cord stem cells. The development could be a massive step forward for the treatment of burn victims or other patients who have suffered severe skin damage.

According to a report, published in the journal Stem Cells Translational Medicine, the research team wrote that they were able to use stem cells derived from the umbilical cord, also known as Wharton stem cells, to generate oral-mucosa or epithelia, two types of tissues needed to treat skin injuries.

The researchers said their novel technique is an improvement on conventional methods that can take weeks to generate artificial skin. To grow the artificial tissue, the study team used a biomaterial made of fibrin and agarose that they had previously designed and developed.

Creating this new type of skin using stem cells, which can be stored in tissue banks, means that it can be used instantly when injuries are caused, and which would bring the application of artificial skin forward many weeks, said study author Antonio Campos, professor of Histology at the University of Granada.

The development builds on previous work by the same team, which was heralded at the World Congress on Tissue Engineering held a few months ago in Seoul, South Korea. The celebrated work pointed to the potential for Wharton stem cells to be turned into epithelia cells.

Last month, a team of Italian scientists announced they had developed a similar method but in reverse. According to their paper in the journal Nature Communications, the team took skin cells from a mouse and reverse programmed them back into stem cells. These stem cells were then used to reduce damages to the nervous system of lab mice.

Our discovery opens new therapeutic possibilities for multiple sclerosis patients because it might target the damage to myelin and nerves itself, said study author Gianvito Martino, from the San Raffaele Scientific Institute in Milan, Italy.

This is an important step for stem cell therapeutics, said Dr. Timothy Coetzee, a lead researcher at the National MS Society who was not directly involved in the research. The hope is that skin or other cells from individuals with MS could one day be used as a source for reparative stem cells, which could then be transplanted back into the patient without the complications of graft rejection.

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Artificial Skin Grown In Lab Using Stem Cells - Science News ...

The breakthrough marks a major advance in treating kidney disease and more avenues in bioengineering human organs. Researchers published their findings in the journal Nature Cell Biology, following their success in making human skin cells form a functioning "mini-kidney" with a width of only a few millimeters.

During self-organization, different types of cells arrange themselves with respect to each other to create the complex structures that exist within an organ, in this case, the kidney, Professor Melissa Little of University of Queenslands Institute for Molecular Bioscience (IMB), who led the study, said in a statement. The fact that such stem cell populations can undergo self-organization in the laboratory bodes well for the future of tissue bioengineering to replace damaged and diseased organs and tissues.

While it may be a while until the process can be used in human trials, Little says it could be a major development in treating chronic kidney disease.

One in three Australians is at risk of developing chronic kidney disease, and the only therapies currently available are kidney transplant and dialysis, Little said. Only one in four patients will receive a donated organ, and dialysis is an ongoing and restrictive treatment regime.

The engineered kidney is a first for science.

"This is the first time anybody has managed to direct stem cells into the functional units of a kidney," Professor Brandon Wainwright, from the University of Queensland, told The Telegraph. "It is an amazing process it is like a Lego building that puts itself together."

Scientists were able to make the kidney by identifying genes that remained active and inactive during kidney development. They were then able to alter the genes into embryonic cells that allowed them to self-organize into the human organ.

"The [researchers] spent years looking at what happens if you turn this gene off and this one on," Wainwright said. "You can eventually coax these stem cells through a journey they [the cells] go through various stages and then think about being a kidney cell and eventually pop together to form a little piece of kidney."

Little predicts the stem cell kidneys could one day be used to make human kidney transplants, or a cluster of mini kidneys used to boost renal function in patients.

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Kidney Grown From Stem Cells For The First Time, Australian Scientists Call Breakthrough ‘An Amazing Process’

Scientists are hoping to increase the size of future kidneys and believe the resulting organs will boost research and allow cheaper, faster testing of drugs. Within the next three to five years, the artificial organs could be used to allow doctors to repair damaged kidneys within the body, rather than letting diseases develop before proceeding with a transplant.

The engineered kidney was developed by a team of Australian scientists led by the University of Queensland's Institute for Molecular Bioscience.

Professor Wainwright said the process for developing the kidney was "like a scientific approach to cooking". The scientists methodically examined which genes were switched on and off during kidney development and then manipulated the skin cells into embryonic stem cells which could "self-organise" and form complex human structures.

"The [researchers] spent years looking at what happens if you turn this gene off and this one on," he said. "You can eventually coax these stem cells through a journey they [the cells] go through various stages and then think about being a kidney cell and eventually pop together to form a little piece of kidney."

The research could eventually help address the demand for transplant organs and improve medical testing of new drugs for patients with kidney disease.

Human kidneys are particularly susceptible to damage during trials, which makes finding effective medicines costly and time-consuming.

Professor Melissa Little, from the University of Queensland, said scientists could try to grow full-grown kidneys for transplants or even "clusters of mini kidneys" that could be transplanted to boost patients' renal functions. But she told The Australian she believed such developments were still more than a decade away.

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Kidney grown from stem cells by Australian scientists

Stem Cell Therapy for Traumatic Brain Injury
Oswaldo Tapenes received multiple injections of human umbilical cord-derived mesenchymal stem cells and his own bone marrow-derived stem cells over the cours...

By: http://www.cellmedicine.com

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Stem Cell Therapy for Traumatic Brain Injury - Video

Orange County, California (PRWEB) December 16, 2013

Top California stem cell clinic, TeleHealth, is now offering stem cell injections for plantar fasciitis. The condition may lead to chronic pain and may not respond to traditional treatments, with the stem cell therapy often allowing for pain relief and the ability to avoid the need for surgery. For more information and scheduling, call (888) 828-4575.

Planter fasciitis affects millions of Americans. The condition leads to chronic heel pain and may make it difficult to participate in recreational activities and even walk normally. Traditional treatments such as physical therapy, NSAIDS, steroid injections and orthotics are often effective over time. However, the condition may not respond as desired to these options and stem cells for plantar fasciitis may be the answer.

Therefore, stem cell injections that TeleHealth provides may offer an excellent option for healing the inflamed area while at the same time providing considerable pain relief. The conventional pain management treatments tend to mask pain, however, they do not actually heal the condition directly.

Regenerative medicine treatments with stem cells maintain the potential of actually healing the damaged tissue to provide long term relief. Telehealth has multiple US Board Certified doctors who have a long history of providing stem cell therapy for numerous conditions including degenerative arthritis, rotator cuff and Achilles tendonitis, ligament injury, elbow soft tissue tendinitis and more.

For those suffering from planter fasciitis or any of the other arthritic or soft tissue injury conditions, call TeleHealth at (888) 828-4575.

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West Coast Stem Cell Clinic, Telehealth, Now Offering Stem Cell Injections for Plantar Fasciitis

Phoenix, Arizona (PRWEB) December 16, 2013

The top Phoenix stem cell treatment clinic, Arizona Pain Stem Cell Institute, is now offering stem cell therapy for plantar fasciitis. The treatments are offered by Board Certified pain management doctors in Arizona, and often help patients avoid surgery. For more information and scheduling, call (602) 507-6550.

Plantar fasciitis affects millions of Americans, causing heel pain that may make it difficult to participate in recreational activities and walking in general. Conventional treatments such as steroid injections, NSAIDS, bracing and physical therapy at times do not relieve the pain properly. Surgery for plantar fasciitis unfortunately does not always provide the desired relief.

Regenerative medicine at the Arizona Pain Stem Cell Institute offers a nonoperative option for plantar fasciitis. This may include stem cell injections with bone marrow, fat derived or amniotic derived material. The procedure is outpatient and low risk.

In addition to treatments for plantar fasciitis, the Institute offers stem cell treatments for degenerative arthritis, tennis elbow, rotator cuff symptoms, achilles tendonitis and more. The procedures are performed by Board Certified pain doctors, with four research projects ongoing.

The Institute is a division of Arizona Pain Specialists, the leading pain center in Arizona. Five locations accept over 50 insurance plans including Workers Compensation, Personal Injury, PPO's, some HMO's and self pay. The regenerative medicine treatments are offered as fee for service.

For more information and scheduling to discuss plantar fasciitis options, call (602) 507-6550.

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Arizona Pain Stem Cell Institute Now Offering Stem Cell Therapy for Plantar Fasciitis

Stemcell treatment for hair and skin, Autologous Adipose Stem Cell Treatment
Through the history of stem cell therapy and stem cell research, animal stem cells have been used, human embryonic stem cells, and now research has led us to...

By: Ojas Aesthetic

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Stemcell treatment for hair and skin, Autologous Adipose Stem Cell Treatment - Video

By Dalia Dangerfield, Reporter Last Updated: Saturday, December 14, 2013, 8:48 PM TAMPA --

USF researchers believe stem cell therapy can help men and women with mild brain injuries.

This is quite a phenomenal observation, said Dr. Cesar Borlongan, a neuroscientist from USF Health. In our hands, stem cell therapy may offer this hope for the soldiers to prevent the progression of the disease and hopefully we can stop the disease process at the early stage."

In a recent study Borlongan injected adult stem cells in rats with traumatic brain injury. The stem cells served as a bridge, allowing new brain cells to move up to the damaged part of the brain.

That's a new concept, it's like the cells are very smart, said Borlongan.

Over time the adult stem cells helped partially repair the brain damage in rats.

Professor Borlongan believes the same may be true for humans allowing them to slowly get better.

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New study shows stem cell therapy helps brain injuries

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Scientists Design and Test New Approach for Corneal Stem Cell Treatments Researchers in the Cedars-Sinai Regenerative Medicine Institute have designed and tested a novel, minute-long procedure to prepare human amniotic membrane for use as a scaffold for specialized stem cells that may be used to treat some corneal diseases. This membrane serves as a foundation that supports the growth of stem cells in order to graft them onto the cornea. This new method, explained in a paper published in the journal PLOS ONE, may accelerate research and clinical applications for stem cell corneal transplantation. CONTACT: Cara Martinez, 310-423-7798; Email cara.martinez@cshs.org; Twitter @CedarsSinaiCara

Cancer Science Evolves, One Consent Form at a Time Tucked away in freezers chilled to minus 80 degrees Celsius are blood and tissue samples from Cedars-Sinai patients. The freezers that hold these samples also contain the hopes of investigators determined to uncover new treatments for cancer patients across the globe. As cancer research continues to evolve, scientists rely on specimen samples, such as tissue, blood or urine, from generous patients to advance discoveries and personalize care. Biobanks, like the state-of-the-art biobank at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, allow patients to make invaluable contributions to medical research and treatment advances that may ultimately be the solution to their own diagnosis or disease down the road. CONTACT: Cara Martinez, 310-423-7798; Email cara.martinez@cshs.org; Twitter @CedarsSinaiCara

Cedars-Sinai, UCLA Health System and Select Medical Announce Partnership to Open Medical Rehabilitation Hospital Cedars-Sinai, UCLA Health System and Select Medical announced today a partnership to create a 138-bed acute inpatient rehabilitation hospital located in the former Century City Hospital. With an expected opening in late 2015, the rehabilitation hospital will serve the growing needs in the community for inpatient rehabilitation, and is also expected to serve as a center for treating complex rehabilitation cases from throughout the nation. The joint venture is an LLC partnership among Cedars-Sinai, UCLA Health System and Select Medical. The vision of the partnership is to develop a world-class regional rehabilitation center providing highly specialized care, advanced treatment, and leading-edge technologies to treat individuals with spinal cord injuries, brain injuries, stroke, amputation, neurological disorders, and musculoskeletal and orthopedic conditions. CONTACT: Sally Stewart, 310-248-6566; Email sally.stewart@cshs.org

Cedars-Sinai Receives Fourth Straight Magnet Recognition for Nursing Excellence from American Nurses Credentialing Center For the fourth time in a row, the American Nurses Credentialing Center has granted Cedars-Sinai the Magnet recognition, the most prestigious designation a healthcare organization can receive for excellence in nursing and patient outcomes. Cedars-Sinai in 2000 became the first Southern California hospital to earn the Magnet honor; it is the only hospital in the state to be granted the designation four times. Cedars-Sinai joins a select list of only 12 hospitals worldwide that have earned Magnet recognition four times. CONTACT: Sally Stewart, 310-248-6566; Email sally.stewart@cshs.org

Ovarian Cancer Discovery Deepens Knowledge of Survival Outcomes Researchers in the Womens Cancer Program at Cedars-Sinais Samuel Oschin Comprehensive Cancer Institute have identified a series of 10 genes that may signify a trifecta of benefits for women diagnosed with ovarian cancer and ultimately reflect improved survival outcomes. The research found that the 10-gene biomarker panel may identify the aggressiveness of a patients disease, help predict survival outcomes and result in novel therapeutic strategies tailored to patients with the most adverse survival outcomes. CONTACT: Cara Martinez, 310-423-7798; Email cara.martinez@cshs.org; Twitter @CedarsSinaiCara

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Cedars-Sinai Medical Tipsheet for Dec. 2013

A new study says heart damage may be reversible with stem cell therapy without dangerous side effects.

STORY HIGHLIGHTS

(CNN) -- On a June day in 2009, a 39-year-old man named Ken Milles lay on an exam table at Cedars-Sinai Medical Center in Los Angeles. A month earlier, he'd suffered a massive heart attack that destroyed nearly a third of his heart.

"The most difficult part was the uncertainty," he recalls. "Your heart is 30% damaged, and they tell you this could affect you the rest of your life." He was about to receive an infusion of stem cells, grown from cells taken from his own heart a few weeks earlier. No one had ever tried this before.

About three weeks later, in Kentucky, a patient named Mike Jones underwent a similar procedure at the University of Louisville's Jewish Hospital. Jones suffered from advanced heart failure, the result of a heart attack years earlier. Like Milles, he received an infusion of stem cells, grown from his own heart tissue.

"Once you reach this stage of heart disease, you don't get better," says Dr. Robert Bolli, who oversaw Jones' procedure, explaining what doctors have always believed and taught. "You can go down slowly, or go down quickly, but you're going to go down."

Conventional wisdom took a hit Monday, as Bolli's group and a team from Cedars-Sinai each reported that stem cell therapies were able to reverse heart damage, without dangerous side effects, at least in a small group of patients.

In Bolli's study, published in The Lancet, 16 patients with severe heart failure received a purified batch of cardiac stem cells. Within a year, their heart function markedly improved. The heart's pumping ability can be quantified through the "Left Ventricle Ejection Fraction," a measure of how much blood the heart pumps with each contraction. A patient with an LVEF of less than 40% is considered to suffer severe heart failure. When the study began, Bolli's patients had an average LVEF of 30.3%. Four months after receiving stem cells, it was 38.5%. Among seven patients who were followed for a full year, it improved to an astounding 42.5%. A control group of seven patients, given nothing but standard maintenance medications, showed no improvement at all.

"We were surprised by the magnitude of improvement," says Bolli, who says traditional therapies, such as placing a stent to physically widen the patient's artery, typically make a smaller difference. Prior to treatment, Mike Jones couldn't walk to the restroom without stopping for breath, says Bolli. "Now he can drive a tractor on his farm, even play basketball with his grandchildren. His life was transformed."

At Cedars-Sinai, 17 patients, including Milles, were given stem cells approximately six weeks after suffering a moderate to major heart attack. All had lost enough tissue to put them "at big risk" of future heart failure, according to Dr. Eduardo Marban, the director of the Cedars-Sinai Heart Institute, who developed the stem cell procedure used there.

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Studies: Stem cells reverse heart damage - CNN.com

London, Dec.12 : Scientists at King's College London have, for the first time, identified the unique properties of two different types of cells, known as fibroblasts, in the skin - one required for hair growth and the other responsible for repairing skin wounds.

The research could pave the way for treatments aimed at repairing injured skin and reducing the impact of ageing on skin function.

Fibroblasts are a type of cell found in the connective tissue of the body's organs, where they produce proteins such as collagen. It is widely believed that all fibroblasts are the same cell type.

However, a study on mice by researchers at King's, published today in Nature, indicates that there are at least two distinct types of fibroblasts in the skin: those in the upper layer of connective tissue, which are required for the formation of hair follicles and those in the lower layer, which are responsible for making most of the skin's collagen fibres and for the initial wave of repair of damaged skin.

The study found that the quantity of these fibroblasts can be increased by signals from the overlying epidermis and that an increase in fibroblasts in the upper layer of the skin results in hair follicles forming during wound healing. This could potentially lead to treatments aimed at reducing scarring.

Professor Fiona Watt, lead author and Director of the Centre for Stem Cells and Regenerative Medicine at King's College London, said: 'Changes to the thickness and compostion of the skin as we age mean that older skin is more prone to injury and takes longer to heal. It is possible that this reflects a loss of upper dermal fibroblasts and therefore it may be possible to restore the skin's elasticity by finding ways to stimulate those cells to grow. Such an approach might also stimulate hair growth and reduce scarring.'

'Although an early study, our research sheds further light on the complex architecture of the skin and the mechanisms triggered in response to skin wounds. The potential to enhance the skin's response to injury and ageing is hugely exciting. However, clinical trials are required to examine the effectiveness of injecting different types of fibroblasts into the skin of humans.'

Dr Paul Colville-Nash, Programme Manager for Regenerative Medicine at the MRC, said: 'These findings are an important step in our understanding of how the skin repairs itself following injury and how that process becomes less efficient as we age. The insights gleaned from this work will have wide-reaching implications in the area of tissue regeneration and have the potential to transform the lives patients who have suffered major burns and trauma.'

This research was funded by the Wellcome Trust, the Medical Research Council and both Guy's and St Thomas' Charity and the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London.

--ANI (Posted on 13-12-2013)

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Skin's own cells offer hope for new ways to repair wounds, reduce impact of ageing

Top Science Stories of 2013

From the first vat-grown hamburger to the discovery of the world's largest volcano, scientists pushed back the limits of human knowledge in 2013 and developed technologies that could radically change how we live our lives.

The Science Media Centre team, in conjunction with our colleagues at the AusSMC, have assembled the top 10 picks for the most significant international science stories of the year. Contact the SMC if you would like more information about any of these stories, including copies of the research papers associated with them.

It was also a big year for New Zealand science with researchers publishing studies in some of the world's most influential journals. See below for our Top 10 list of New Zealand science stories that captured the public's attention in 2013.

Top 10 international science stories

1. Space sounds revealed Voyager 1 had boldly gone: In September, NASA's Voyager 1 spacecraft became the first man-made object to leave our solar system and venture into interstellar space. The probe, launched in 1977 with the aim of reaching Jupiter and Saturn, is now over 19 billion kilometres from the sun. Scientists listened in to vibrations in the plasma surrounding Voyager - the sound of interstellar space - after it was hit by a massive solar wave in April. The vibrations allowed them to calculate the plasma's density, which differs between our solar system and interstellar space, confirming Voyager was no longer in our solar system.

2. Carbon dioxide hit a new peak and human influence on the climate was clearer than ever:In May, levels of carbon dioxide in the Earth's atmosphere reached a symbolic milestone, passing 400ppm (parts per million) for the first time in human history. Just a few months later in September, the leading international body for the assessment of climate change, the Intergovernmental Panel on Climate Change (IPCC), found that human influence on the climate system is clearer than ever -we are now 95 percent certain that humans are the cause of global warming. Climate scientists from New Zealand were among the more than 600 scientists and researchers who worked on the IPCC report. 3. Scientists created human stem cells using cloning techniques: In May, researchers used therapeutic cloning to create human embryonic stem cells for the first time. The process involved taking the nucleus - which contains the genetic material - from a normal cell and transferring it into an unfertilised egg with its own genetic material removed. While this approach had previously been used in monkeys and mice, it had never succeeded using human cells. This discovery, described by Australian scientists as "a major breakthrough in regenerative medicine", could help develop personalised therapies for a range of currently untreatable diseases. However, the process requires human donor eggs, which are not easy to obtain, and raises a number of ethical issues.

4. Do you want fries with that? The world's most expensive burger was grown in the lab: The world's first lab-grown burger was cooked and eaten at a news conference in London in August this year - generating headlines around the world. The burger patty - which one food critic described as 'close to meat' - was developed by scientists from Maastricht University in the Netherlands through research funded by Google co-founder Sergey Brin. Starting with stem cells from a biopsy of two cows (a Belgian Blue and a Blonde d'Aquitaine), the scientists grew muscle fibres in the lab. The fibres were pressed together with breadcrumbs and binding ingredients, then coloured with beetroot juice and saffron, resulting in the most expensive hamburger in history at a cost of around NZ$400,000.

5. Doctors stopped HIV in its tracks in the "Mississippi baby": A child born with HIV and treated with a series of antiviral drugs for the first 18 months of its life was found to be free of the virus more than 12 months after treatment ended. When the infant was 30 months of age, HIV-1 antibodies remained completely undetectable. However, the big question of whether this child, known as the "Mississippi baby", has truly been cured of HIV remains unanswered. "The best answer at the moment is a definitive maybe", HIV expert Scott Hammer, wrote in a New England Journal of Medicineeditorial which accompanied the research.

6. Redefining mental illness: In May, the new version of the diagnostic reference manual used by clinicians in the U.S. and around the world to diagnose mental disorders was released. The fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) is the first update in nearly 20 years and followed a decade of review and consultation. It's publication met with widespread controversy. One of its major changes is to introduce a graded scale known as Autism Spectrum Disorder combining the former four autism-related disorders: autistic, Asperger's, childhood disintegrative, and pervasive developmental disorder. Elsewhere, several new disorders were added, new suicide risk assessment scales were introduced and the threshold for diagnosing Post Traumatic Stress Disorder (PTSD) was lowered. Critics of DSM-5, including New Zealand experts, argue that it will lead to the over-diagnosis of mental disorders, stigmatising millions of people who are essentially normal.

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Top Science Stories of 2013

Parkinson's patient Ed Fitzpatrick speaks about stem cell research for his disease. Fitzpatrick talked on a Dec. 7 panel at the World Stem Cell Summit in San Diego. Bradley J. Fikes

Parkinson's patient Ed Fitzpatrick speaks about stem cell research for his disease. Fitzpatrick talked on a Dec. 7 panel at the World Stem Cell Summit in San Diego.

For eight local Parkinsons patients seeking treatment with stem cell technology, 2014 could bring the milestone theyve been anticipating.

If all goes well, the U.S. Food and Drug Administration will approve an attempt to replace the brain cells destroyed in Parkinsons. The new cells, grown from each patients own skin cells, are expected to restore normal movement in the patients.

Because the new brain cells are made from the patients own cells, immunosuppressive drugs shouldnt be needed. Ideally, patients could stop taking their medications and resume normal activities for many years, or even the rest of their lives.

The project, Summit4StemCell.org, is a collaboration between three nonprofits. The Scripps Research Institute handles the science; Scripps Clinic takes care of the medical side; and the Parkinsons Association of San Diego helps to raise money for the self-funded project.

Since 2011, the focus has been at the institute, where scientists led by Jeanne Loring have made the artificial embryonic stem cells, called induced pluripotent stem cells, and turned them into the needed brain cells. Now Scripps Clinic is assuming a more prominent role to prepare for treating the patients.

A study in rats began in early December; results are expected by April. The animal study is meant to assess safety, although researchers will also look for signs of effectiveness.

In January, scientists will visit the FDA to lay the groundwork for a formal application, said Scripps Clinic neurologist Melissa Houser, who treats all eight patients.

Success in the animal study will likely result in a go-ahead, Houser said. If the animal trial fails, its back to the drawing board.

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Parkinson’s stem cell project aims for 2014 approval

PUBLIC RELEASE DATE:

12-Dec-2013

Contact: Shaun Mason smason@mednet.ucla.edu 310-206-2805 University of California - Los Angeles

Stem cell researchers from UCLA have published the first study to identify the origin cells and track the early development of human articular cartilage, providing what could be a new cell source and biological roadmap for therapies to repair cartilage defects and damage from osteoarthritis.

Such transformative therapies could reach clinical trials within three years, said the scientists from UCLA's Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research.

The study, led by Dr. Denis Evseenko, an assistant professor of orthopedic surgery and head of UCLA's Laboratory of Connective Tissue Regeneration, was published online Dec. 12 in the journal Stem Cell Reports and will appear in a forthcoming print edition.

Articular cartilage, a highly specialized tissue formed from cells called chondrocytes, protects the bones of joints from forces associated with load-bearing and impact and allows nearly frictionless motion between the articular surfaces the areas where bone connects with other bones in a joint.

Cartilage injury and a lack of cartilage regeneration often lead to osteoarthritis, which involves the degradation of joints, including cartilage and bone. Osteoarthritis currently affects more than 20 million people in the U.S., making joint-surface restoration a major priority in modern medicine.

While scientists have studied the ability of different cell types to generate articular cartilage, none of the current cell-based repair strategies including expanded articular chondrocytes or mesenchymal stromal cells from adult bone marrow, adipose tissue, sinovium or amniotic fluid have generated long-lasting articular cartilage tissue in the laboratory.

For the current study, Evseenko and his colleagues used complex molecular biology techniques to determine which cells grown from embryonic stem cells, which can become any cell type in the body, were the progenitors of cartilage cells, or chondrocytes. They then tested and confirmed the growth of these progenitor cells into cartilage cells and monitored their growth progress, observing and recording important genetic features, or landmarks, that indicated the growth stages of these cells as they developed into the cartilage cells.

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UCLA stem cell scientists first to track joint cartilage development in humans

Poway, California (PRWEB) December 13, 2013

Noni is a ten-year-old released Canine Companion for Independence dog who just achieved her Master Agility Champion status after the pain from arthritis tried to slow her down. Nonis owner, Dr. Kim Dembinski, a veterinarian at Paradise Veterinary Hospital in San Diego turned to stem cell therapy by Vet-Stem, Inc. and fellow colleague Dr. Jennipher Harris to help Noni.

When Dr. Dembinski noticed weakness and discomfort in her aging agility dog she was proactive in keeping Noni happy and comfortable, The main thought was that she gives so much between therapy work, being my best friend, and as the clinic mascot that giving her relief from pain and her being more comfortable was the least I could do for her.

Nonis stem cell therapy involved a small fat sample collection, which was brought to Vet-Stems lab in Poway, California. There, highly trained lab technicians processed Nonis fat tissue to isolate the stem cells into doses that could be injected into the arthritic joints that were causing her pain. Normally the tissue is shipped overnight to Vet-Stem and the cells are shipped overnight back to the veterinarian making doses available within 48 hours, but because Paradise Veterinary Hospital is located near Vet-Stem Nonis stem cell doses were available for injection the same day the fat sample was collected.

Noni did very well post procedure; she regained muscle strength and flexibility, Dr. Dembinski reported, Noni did four weeks of rehab then went right back to competing in agility. Six months after the procedure she earned her MACH (Master Agility Champion), AKC (American Kennel Club) title. Because of her stem cell therapy she is still comfortable and playing agility!

Dr. Dembinski is a general practitioner for pets including dogs, cats, small mammals, birds and exotics. She is currently owner and primary veterinarian at Paradise Veterinary Hospital and sits on the board of the San Diego County Veterinary Medical Association. Caring for animals is not just a job for Dr. Dembinski, it is a passion. In her free time she and Noni compete in dog agility trials with AKC, North American Dog Agility Council and Canine Performance Events.

About Vet-Stem, Inc. Vet-Stem, Inc. was formed in 2002 to bring regenerative medicine to the veterinary profession. The privately held company is working to develop therapies in veterinary medicine that apply regenerative technologies while utilizing the natural healing properties inherent in all animals. As the first company in the United States to provide an adipose-derived stem cell service to veterinarians for their patients, Vet-Stem, Inc. pioneered the use of regenerative stem cells in veterinary medicine. The company holds exclusive licenses to over 50 patents including world-wide veterinary rights for use of adipose derived stem cells. In the last decade over 10,000 animals have been treated using Vet-Stem, Inc.s services, and Vet-Stem is actively investigating stem cell therapy for immune-mediated and inflammatory disease, as well as organ disease and failure. For more on Vet-Stem, Inc. and Veterinary Regenerative Medicine visit http://www.vet-stem.com or call 858-748-2004.

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San Diego Canine Overcomes Pain to Achieve Championship with the Help of Paradise Veterinary Hospital and Vet-Stem, Inc.

Current ratings for: Brain cancer treatment may lie in reactivating immune cells

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When they examined tumor samples of glioblastoma, the deadliest form of brain cancer, researchers in Canada discovered they contained deactivated forms of specialized immune cells that normally fight tumor-generating cells. When they tested a drug that reactivates these immune cells in diseased mice, the animals lived two to three times longer.

The researchers, from the University of Calgary's Hotchkiss Brain Institute (HBI) and Southern Alberta Cancer Research Institute, hope their discovery will lead to clinical trials and eventually to a new standard of care for brain tumor patients.

They write about their findings in a recent online issue of Nature Neuroscience.

Even though treatments already exist, the median survival for patients with glioblastoma is only 15 months - fewer than 1 in 20 survive more than 5 years.

Our brains have their own specialized immune cells called microglia that protect against injury and infection.

They are the brain's "dedicated immune system," explains senior author V. Wee Yong, a professor in Calgary's Departments of Oncology and Clinical Neurosciences.

As with other cancers, brain tumors start from stem cells. In the case of brain tumors, they are called brain tumor initiating cells (BTICs).

BTICs grow and divide rapidly, eventually forming a mass, the tumor itself.

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Brain cancer treatment may lie in reactivating immune cells

Phoenix, Arizona (PRWEB) December 11, 2013

The top Phoenix stem cell treatment clinic, Arizona Pain Stem Cell Institute, is now offering four stem cell therapies for arthritis. The treatments offered are very low risk and offered as an outpatient. For more information and scheduling on the regenerative medicine treatments offered, call (602) 507-6550.

The Board Certified, Award Winning pain management doctors in Arizona provide either bone marrow, fat derived or amniotic stem cell injections. The fat or bone marrow is harvested from the patient, and immediately processed for injection into the target area. Since the material comes directly from the patient, the risks are exceptionally low.

With regards to the amniotic derived injections, the fluid is obtained from consenting donors and processed at an FDA regulated lab. The treatment does not involve any fetal tissue, and contains a high concentration of stem cells, growth factors and anti-inflammatory factors.

The additional treatment offered is platelet rich plasma therapy, known as PRP therapy for short. PRP therapy involves a simple blood draw from the patient, which is then centrifuged and spun down for 15 minutes to obtain a solution rich in platelets and growth factors.

The PRP is then injected into the target area, where published studies have shown impressive results for arthritis and soft tissue injury such as rotator cuff tendonitis, tennis elbow, Achilles tendonitis, ligament injury and more. The treatments have the potential to not only provide pain relief, but also regenerate the damaged tissue or cartilage.

Numerous athletes over the past few years have turned to regenerative medicine to obtain pain relief and get back into playing condition. This has included athletes such as Hines Ward, Tiger Woods, Kobe Bryant, Rafael Nadal and many more.

The Arizona Pain Stem Cell Institute treats everyone from athletes to college students to executives, manual laborers, senior citizens and more. Board Certified and Award Winning Phoenix pain management doctors offer the stem cell treatments along with other cutting edge pain relief options such as radiofrequency ablation and spinal cord stimulator implants.

Over 50 insurance plans are accepted, and Arizona Pain Specialists offers 5 locations for convenience. Call (602) 507-6550 for scheduling.

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Phoenix Pain Management Doctors at Arizona Pain Stem Cell Institute Now Offering 4 Stem Cell Treatments for Arthritis